The bactericidal and fungicidal activity of some derivatives of aniline and of glycine having, on the nitrogen atom, a variously substituted phenyl and an acyl group of various nature has been recently described. In particular, said acyl group may consist of an alpha or beta-haloalkanoyl (German pa tent application DOS 2,513,789, Ciba Geigy), or of an acetyl group substituted in alpha by an atom of sulphur or of oxygen bound, in its turn, to groups of various nature (French patent application No. 7,510,722, Ciba Geigy), or, furthermore, of a 2-furoyl group, a 2-thienoyl group or a pyridyl 2-carboxylic group (German patent applications DOS 2,513,732 and 2,513,788, Ciba Geigy).
The microbicidal activity of methylalaninates carrying, on the nitrogen atom, a 2,6-dialkyl-phenyl and one of the following groups: cyclopropanoyl, acryloyl, crotonyl, has been described too (Swiss patent applications, 4,998/74, 2,906/75).
The interest in the research of new derivatives of acyl anilines having a fungicidal action derives from the necessity of finding in them a high fungicidal activity combined with the absence of phytotoxicity. In fact, some products already known, though exhibiting an excellent fungicidal action, also exhibit toxicity for the plants to be protected from the infections due to fungi.
The present invention relates to new acyl anilines and more particularly to new acyl anilines having a fungicidal action, to use and the preparation of same.
We have now found new fungicidal acyl anilines--which are an object of this invention--corresponding to the general formula: ##STR5## wherein R and R.sup.1 (like or unlike each other)=H; CH.sub.3 ; C.sub.2 H.sub.5 ; n.C.sub.3 H.sub.7 ; --CH.sub.2 -CH.dbd.CH.sub.2 ; --CH.dbd.CH--CH.sub.3 ;
R.sup.3 and R.sup.4 (like or unlike each other)=H; alkyl C.sub.1 -C.sub.3 ; halomethyl; Cl; F; CN; O-alkyl; S-alkyl; alkoxymethyl; PA1 or R.sup.3 and R.sup.4 together are (CH.sub.2 .dbd.) ##STR6## (R.sup.9 =alkyl C.sub.1 -C.sub.3); CN; --CH(OR.sup.5).sub.2 (R.sup.5 =alkyl or alkylidene); ##STR7## (R.sup.6 and R.sup.7 =H, alkyl) n=0,1 PA1 Z=phenyl optionally substituted; ##STR8## and R.sup.2 =H, CH.sub.3 ; m=1,2; Y=alkynyl C.sub.2 -C.sub.8 ; phenyl optionally substituted; phenylacetyl; furyl, thienyl; pyridyl; heterocyclic groups containing 2 or 3 heteroatoms, one of them different from nitrogen; PA1 R.sup.8 =CH.sub.3 ; alkoxymethyl; halomethyl; O-alkyl.
The compounds of formula I are endowed with a high fungicidal activity and with a low phytotoxicity.
The synthesis of the acyl anilines corresponding to general formula (I) is generally carried out by condensing anilines of general formula: ##STR9## (in which, X,R,R.sup.1, R.sup.3, R.sup.4 and n have the meanings specified hereinbefore) with a compound of formula ##STR10## (wherein Z has the meanings specified hereinbefore) in the presence of an halogenhydric acid-accepting base or dimethylformamide.
Some of the anilines of general formula II are available on the market, others are easily obtained by known reactions starting from 2,6-disubstituted anilines. The anilines substituted in one or both the 2 and 6 positions by alkenyl groups have been described in Italian Patent Applications n. 23809 A/77 and 28817 A/77. As examples of compounds of general formula III can be mentioned: benzoyl chloride, phenylacetylchloride, the monochloride of a melonic ester (Cl--CO--CH.sub.2 --COO--alkyl), the chloride of chloro-acetoaceticacid (Cl--CO--CH.sub.2 --CO--CH.sub.2 Cl) etc.
The synthesis of compounds of formula I wherein Z=CH.sub.2 --CO--R.sup.8 and R.sup.8 =CH.sub.3, can also be obtained by reacting an aniline of general formula II with diketene ##STR11## The compounds reported on Table 1 have been prepared according to the methods hereinabove described.
TABLE 1 __________________________________________________________________________ (a) ELEMENTAL ANALYSIS (%) COM- m.p. calculated found POUND FORMULA (.degree.C.) C H N C H N __________________________________________________________________________ ##STR12## 96-100 73,29 6,80 4,50 73,8 7,0 4,4 2 ##STR13## 97-100 74,31 7,42 4,13 74,45 7,77 4,25 3 ##STR14## 114- 115 4 ##STR15## 78-80 78,32 7,12 4,30 75,34 7,47 4,67 5 ##STR16## oil 73,37 7,70 4,18 75,4 8,4 4,3 6 ##STR17## 58-59 72,81 7,40 4,47 73,14 7,66 4,69 7 ##STR18## oil 74,28 6,54 4,33 73,6 6,6 4,6 8 ##STR19## 63-64 65,23 6,39 4,23 66,53 6,74 4,54 9 ##STR20## 105-108 70,36 6,79 4,10 70,5 6,9 4,0 10 ##STR21## oil 74,76 7,70 3,96 73,84 7,91 3,99 11 ##STR22## 56-57 12 ##STR23## 51-52 74,31 7,42 4,13 74,03 7,52 4,07 13 ##STR24## oil 74,31 7,42 4,13 72,96 7,16 4,34 14 ##STR25## 69-70 73,82 7,12 4,30 73,41 7,28 4,31 (d) 15 ##STR26## 97-100 65,99 5,83 4,05 67,0 5,9 3,7 16 ##STR27## 60-64 72,47 8,82 4,22 71,75 9,12 3,81 17 ##STR28## 90-93 70,96 7,09 3,94 70,59 7,28 3,70 (e) 18 ##STR29## oil (e) 19 ##STR30## oil 20 ##STR31## oil 64.85 6.95 4.20 64.84 7.24 4.51 21 ##STR32## oil 66.83 7.01 3.90 67.93 7.72 4.67 22 ##STR33## oil 23 ##STR34## 24 ##STR35## 25 ##STR36## 105-110 26 ##STR37## oil 69.95 7.34 4.08 68.60 7.30 4.32 27 ##STR38## oil 68.12 7.30 4.41 65.85 7.49 4.35 28 ##STR39## oil 67.69 7.89 4.38 67.71 8.32 4.40 29 ##STR40## oil 68.12 7.30 4.41 67.70 7.33 4.36 30 ##STR41## oil 67.31 6.98 4.62 66.2 6.90 4.90 31 ##STR42## 84-87 32 ##STR43## oil 62.12 7.49 4.53 61.06 7.84 4.47 33 ##STR44## oil 66.43 8.20 4.56 65.76 8.43 4.89 (e) 34 ##STR45## 65-68 35 ##STR46## oil 68.55 6.71 4.44 67.61 6.70 4.57 __________________________________________________________________________ (b) (c) COM- IR.sub.max NMR POUND FORMULA (cm.sup.-1) (.delta. ppm) [TMS] __________________________________________________________________________ ##STR47## 1635 1730 1745 1,04 (d,3H,CH.sub.3CH) 2,23 (s,3H,CH.sub.3.phi.) 2,29 (s,3H,CH.sub.3.phi.) 3,79 (s,3H,CH.sub.3O) 4,30 (q,1H,CH) 6,83-7,33 (m,8H,aromatic protons) 2 ##STR48## 1630 1715 1720 1,2(d,3H,CH.sub.3CH) 1,3[d,6H,(CH.sub. 3).sub.2CH] 2,3 (s,3H,CH.sub.3.phi.) 2,32 (s,3H,CH.sub.3.phi.) 4,4 (q,1H,CH.sub.3CH) 5,2[m,1H,(CH.sub.3). sub.2 CH] 6,8-7,5 (m,8H,aromatic protons) 3 ##STR49## 1,20 (d,3H,CH.sub.3CH) 2,27 (s,3H,CH.sub.3.phi.) 2,37 (s,3H,CH.sub.3.phi.) 2,47 (s,3H,CH.sub.3.phi.) 3,83 (s,3H,CH.sub.3O) 4,30 (q,1H,CH.sub.3CH) 6,63-7,20 (m,7H, aromatic protons) 4 ##STR50## 1660 1750 0,98 (d,3H,CH.sub.3CH) 1,85 (s,3H,CH.sub.3.phi.) 2,4 (s,3H,CH.sub.3.phi.) 3,25 (s,2H,CH.sub.2 3,8 (s,3H,CH.sub.3O) 4,45 (q,1H,CH.sub.3CH) 6,85-7,3 (m,8H, aromatic protons 5 ##STR51## 6 ##STR52## ##STR53## 7 ##STR54## 1,35; 1,65 (d,d,3H,CH.sub.3CH) 3,3 (m,2H,CH.sub.2CHCH.sub.2) 3,8 (s,3H,CH.sub.3O) 4,8 (q,1H,CH.sub.3CH) 4,9; 5,15 (m,m,2H,CHH.sub.2) 5,6 (m,1H CHCH.sub.2) 7,1-7,35 (m,9H, aromatic protons) 8 ##STR55## 1665 1745 1,0 (d, 3H, CH.sub.3CH) 2,0 (s,3H,CH.sub.3.phi.) 2,45 (s,3H,CH.sub.3.phi.) 3,4 (s,2H,CH.sub.2) 3,8 (s,3H,COOCH.sub.3) 4,5 (q,1H,CH.sub.3CH) 6,5-7,3 (m,6H) 9 ##STR56## 1630 1750 1,3 (d, 3H, CH.sub.3CH) 2,3 (s, 6H, CH.sub.3.phi.) 3,7 (s, 3H, CH.sub.3O.phi.) 3,85 (s, 3H, COOCH.sub.3) 4,45 (q, 1H,CH.sub.3CH) 6,75-7,6(m, 7H, aromatic protons) 10 ##STR57## 1650 1730 1,2-1,45(9H) 2,3 (s, 6H, CH.sub.3.phi. 4,4 (q,lH, NCH) 5,2 (m,-1H, COOCH) 6,8-7,5 (m, 8H, aromatic protons) 11 ##STR58## 2,05 (s,6H,CH.sub.3.phi.) 3,4 (s,2H,CH.sub.2.phi.) 3,85 (s,3H,COOCH.sub.3) 4,6-5,4 (d,d,2H,CH.sub.2C) 7,1-7,3 (m,8H, aromatic protons) 12 ##STR59## 13 ##STR60## 14 ##STR61## (d) 15 ##STR62## 1630 1730 1745 1,27 (d,3H,CH.sub.3CH) 2,3 (s,6H,CH.sub.3.phi.) 3,8 (s,3H,COOCH.sub.3) 4,45 (q,1H,CH.sub.3H) 6,9-7,4 (m,7H, aromatic protons) 16 ##STR63## 1650 1750 17 ##STR64## 1655 1745 (e) 18 ##STR65## ##STR66## (e) 19 ##STR67## ##STR68## 20 ##STR69## 1660 1745 21 ##STR70## 1660 1745 22 ##STR71## ##STR72## 23 ##STR73## 0.97-0.99 (3H,d,d,CH.sub.3CH) 1.27 (3H,t,CH.sub.3CH.sub.2) 2.27-2.46 (3H,s,s,CH.sub.3.phi.) 2.85 (2H,s,CH.sub.2CO) 2.27-3.17 (2H,mCH.sub.2CH.sub.3) 3.60-3.72 (6H,s,s,OCH.sub.3) 4.37 (1H,m,CH.sub.3H) 6.93-7.30 (3H,m, aromatic protons) 24 ##STR74## 0.97 (3H,d,CH.sub.3CH) 1.23 (6H,t,CH.sub.3CH.sub.2) 2.83 (2H,s,CH.sub.2CO) 2.13-3.17 (4H,m,CH.sub.2CH.sub.3) 3.57-3.70 (6H,s,s,OCH.sub.3) 4.33 (1H,m,CHCH.sub.3) 6.97-7.37 (3H,m, aromatic protons) 25 ##STR75## 26 ##STR76## 1630 1650 1720 1745 27 ##STR77## 1630 1650 1715 1745 28 ##STR78## 1630 1655 1740 29 ##STR79## 1630 1750 30 ##STR80## 1630 1650 1720 1740 31 ##STR81## 32 ##STR82## 1660 1745 33 ##STR83## (e) 34 ##STR84## ##STR85## 35 ##STR86## 1655 1740 1.0 (d,3H,CH.sub.3CH) 2.1 (s,3H,CH.sub.3.phi.) 2.4 (s,3H,CH.sub.3.phi.) 3.3 (s,2H,CH.sub.2 CO) 3.8 (s,3H,OCH.sub.3) 4.4 (q,1H,CH.sub.3CH) 5.9-7.5 (m,6H, aromatic protons) __________________________________________________________________________ Notes to Table 1 (a) The melting points have not been corrected. (b) Only the most meaningful bands are recorded. (c) The NMR spectra of compounds 1 and 3 have been recorded by using CCl.sub.4 as a solvent, the other spectra by using CDCl.sub.3 ; s = singlet, d = doublet, t = triplet, q = quadruplet, m = multiplet. (d) Elemental analysis: calculated chlorine = 10.25; found chlorine = 9.68. (e) Mixture of tautomers
The compounds of general formula I are endowed with an excellent fungicidal activity towards phytopathogenous fungi, and the action exerted by same is both preventive (as it prevents the desease from arising) and curative (i.e. when the infection is already in progress). Furthermore they possess good systemic characteristics (i.e. they are transported to the various parts of the plant) wherefore it is possible to apply them through the leaves or the soil.
The fungicidal activities of some compounds of this invention towards vine mildew [Plasmopara viticola (B. et C.) Berl et de Toni], tobacco mildew [Peronospora tabacina Adam] and tomato mildew [Phytophthora infestans] respectively, are recorded on tables 2, 3 and 4.
The fungicidal activity of the compounds according to the present invention has been evaluated as described in examples 14 to 22 and has been expressed in tables 2, 3 and 4 by a scale of values from 100 (total activity, sound plant) to 0 (no activity, thoroughly infected plant).
The data obtained from a comparison with Zineb, a commercial fungicide widely utilized, prove that the compounds of the present invention are by far more active, the doses being equal.
TABLE 2 __________________________________________________________________________ Fungidical activity against Plasmopara viticola on vine Immunizing Prevent. Curative Systemic Type of on on on upper Systemic action leaves leaves leaves soil Compound Treatment days (a) days (a) days (a) days (a) No. Dose (%) 1 7 1 7 1 7 1 7 __________________________________________________________________________ 18 (b) 1 100 100 100 100 100 100 100 100 0.5 100 100 100 100 100 100 0.1 100 100 100 100 100 19 (c) 1 100 100 100 0.5 100 0.1 100 Zineb 1 90 (refer- 0.5 70 ence com- mercial 0.1 30 fungi- cide) __________________________________________________________________________ (a) days elapsed from the treatment to the infection or viceversa. (b) N(2,6-dimethylphenyl)-N-acetacetyl-.alpha.-amino-methylpropionate. (c) N(2,6-dimethylphenyl)-N-acetacetyl-.alpha.-amino-ethylpropionate.
TABLE 3 ______________________________________ Fungicidal activity against Peronospora tabacina Type of action Preventive Curative Compound Treatment on leaves on leaves No. Dose (%) days.sup.(a) 2 days.sup.(a) 2 ______________________________________ 18.sup.(b) 1 100 100 0.5 100 100 ______________________________________
TABLE 4 ______________________________________ Fungicidal activity against Phytophthora infestans on tomato Type of action Preventive Curative Systemic Compound Treatment on leaves on leaves soil No. Dose (%) days.sup.(a) 1 days.sup.(a) 1 days.sup.(a) 3 ______________________________________ 18.sup.(b) 1 100 100 100 0.5 100 100 100 0.1 -- -- 100 ______________________________________ .sup.(a) days elapsed from the treatment to the infection or viceversa. .sup.(b) N-(2,6-dimethylphenyl)-N-acetacetyl-.alpha.-amino-methylpropionate.
Table 5 shows the fungicidal activity of some new acyl anilines within the scope of the present invention and the phytotoxicity of same. Both these data are compared with those of "Furalaxyl", a known product described in German patent application No. 2,513,788 and "Ridomil" described in German patent application No. 2,515,091. The values concerning the fungicidal activity and the phytotoxicity have been determined as described in examples 23 and 15. From the comparison between the recorded data it is clear that, with equal application doses, the compounds of this invention exhibit a fungicidal activity equal to the one of "Furalaxyl" and "Ridomil", but a by far lower phytotoxicity.
TABLE 5 ______________________________________ Curative activity against Plasmopara viticola on vine, by application to leaves ef- Phytotoxici- Products fected 24 h after infection, ty index at (see Table 1) at doses of 0.1.permill. doses of 3.permill. ______________________________________ 1 100 25 2 100 0 3 100 5 4 100 10 Ridomil* 100 100 "Furalaxyl"* 100 100 (check pro- ducts) ______________________________________ *"Furalaxyl" = N-(2,6-dimethylphenyl)-N-(1'-carbomethoxy-ethyl)-2-furoylamide ##STR87## *"Ridomil" = N-(2,6-dimethylphenyl)-N-(1'-carbomethoxy-ethyl)-methoxyacetamide ##STR88##
The damages caused by phytotoxicity to the plants cannot be avoided by using the dose of fungicidal product, which results to be the best compromise between the fungicidal activity of the product and its phytotoxicity. In fact in the practical application in agriculture, the fungicidal product amount which actually remains on the plant varies even remarkably in relation to weather conditions (especially frequency of precipitations), to the correctness and frequency of the treatments effected by the farmer. It is therefore necessary to have available fungicidal products endowed with a good activity as well as with a wide margin of safety, so that even high doses of product cannot damage the plants.
The following Table 6 shows a comparison between the fungicidal activity of some compounds object of the present invention and the activity of "Furalaxyl" and of "Ridomil" at different application doses, and the phytotoxicity of the same compounds at increasing doses.
From the comparison between the data recorded on Table 6 it is evident that the fungicidal activity of the compounds of this invention is of the same order of magnitude as the one of the check compounds, but the phytotoxicity is substantially lower as the application dose increases.
TABLE 6 ______________________________________ Curative activity against Plasmopara vitivola on vine at indicated Phytotoxicity index at the Compound doses (.permill.) indicated doses (.permill.) (see Table 1) 0.1 0.05 0.01 0.005 0.75 1.5 3 9 ______________________________________ 1 100 98 76 41 25 2 100 80 70 60 0 0 4 100 100 100 100 0 0 10 37 8 100 100 100 100 30 Furalaxyl 100 100 100 100 32 53 100 100 Ridomil 100 100 100 100 30 54 100 100 ______________________________________